Plant-derived phenolics as regulators of nitric oxide production in microglia: mechanisms and therapeutic potential

Neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases with microglial activation and excessive nitric oxide production contributing significantly to disease progression. Plant-derived phenolic compounds have emerged as promising neuroprotective agents due to their ability to modulate the key signaling pathways, including nuclear factor-κB, mitogen-activated protein kinases, nuclear factor erythroid 2-related factor 2, and phosphoinositide 3-kinase/protein kinase B. These bioactive molecules effectively suppress inducible nitric oxide synthase expression, reduce oxidative and nitrosative stress, and restore immune homeostasis. Additionally, these natural phenolic compounds are able to regulate mitochondrial function and autophagy, further supporting their therapeutic potential in central nervous system disorders. The presented review aimed to explain the key known mechanisms of action of plant-origin phenolics, in order to evaluate their potential in developing treatments and preventing central nervous system diseases.